The proposed studies will systematically explore the effects of pressure overload hypertrophy, developing in a physiologic model of arterial hypertension, on the contractile properties of heart muscle. The animal model to be used is the two-kidney renovascular hypertensive rat which develops hypertrophy over a 30 week period and fully egresses 10 weeks following relief of the hypertension. The isolated left ventricular papillary muscle and perfused left ventricle will be studied relative to the following questions: 1) Is there a contractile defect or dynamic compliance alteration in this form of pressure-overload hypertrophy? 2) Is resting compliance altered and is this related to changes in connective tissue (hydroxy proline)? 3) Is activation and relaxation altered? 4) How do these changes relate to the extent of hypertrophy judged from ultrastructurally determined cell area measurements? and 5) Is the process reversible on single or multiple occasions? Contractile properties will be studied in terms of mechanical behavior including force-length relations, force-velocity curves, velocity-length relations and relaxation dynamics. The data will be normalized for muscle crossection and extent of hypertrophy. Excitation-contraction coupling properties will be studied in terms of force-frequency and Ca ions force curves; agents which after cellular movements of Ca ion (e.g., D600 and Ryanodine) will be used to elicit subtle changes induced by hypertrophy in activating membrane systems as well as in relaxation processes. Pressure-overload hypertrophy will be regressed by either removal of the renal artery clip or with a new orally administered, inhibitor of angiotension-converting enzyme, SQ14225. The effect of repetitive bouts of hypertension, induced by programmed withdrawal of SQ14225 on contractile performance and myocardial collagen content will also be explored.